Nasopharyngeal cancer (NPC) is common in Southeast Asia and Southern China. It is infiltrated by T-regulatory cells and shows high expression of PD-L1. However, monotherapy PD-1/PD-L1 activity is limited and not superior to salvage combination chemotherapy. We hypothesized that CTLA-4 blockade would suppress T-regulatory function and complement PD-1 blockade. We update the efficacy and safety from the first phase II study of this combination in NPC.
A single arm phase II of a Simon 2-stage design was used, with preplanned expansion for safety and efficacy. Pts were treated with Nivolumab 3 mg/kg q2 weeks, and Ipilimumab 1 mg/kg q6 weeks. Eligible pts had R/M NPC, measurable plasma EBV DNA, no more than 1 prior line of chemotherapy, ECOG 0-1, and adequate organ function. All pts who met the eligibility criteria and received at least one dose of the combination drugs were included in the safety and efficacy analysis. The primary efficacy endpoint was best overall response (BOR) by RECIST 1.1. Toxicity was assessed using CTCAE criteria.
Forty pts were enrolled between July 2017 and September 2019 across Taiwan and Singapore (data cut-off February 2020). Median age was 53 years (23-73 years). Most (90.0%) were of Chinese ethnicity and 33 (82.5%) were male. Thirty-nine pts (97.5%) had prior chemotherapy treatment. Six (15%) pts remain on study. The median number of cycles received was 4. Overall, 12 pts had a BOR of PR (30%; 95% CI 16.6%-46.5%). The median duration of response (DOR) was 5.9 months (95% CI 3.95-8.97 months). With a median follow up of 17.3 months, median PFS was 5.3 months (95% CI 3.0-6.4 months) and median OS was 17.6 months (95% CI 13.1-30.0). Thirty-four pts (85%) experienced treatment-related (Tr) events. Common TrAEs included maculopapular rash (n=16; 40%) and hypothyroidism (n=11; 28%). Four (10%) pts experienced Grade 3/4 TrSAEs including hypocortisolism, pneumonia, myasthenia gravis, and raised lipase. There was no relationship of tumor mutation burden/PD-1 expression to response.
Combination Nivolumab/Ipilimumab is active and safe in NPC, with durable responses and PFS, presenting a possible alternative to salvage chemotherapy.
Clinical trial identification
Legal entity responsible for the study
Bristol-Myers Squibb; Ono pharmaceuticals.
All authors have declared no conflicts of interest.